Multiple Myeloma
Conditions
Brief summary
Multiple myeloma is the second most common hematologic malignancy in adults and despite the new therapies that have been developed in the last decades it remains incurable. Over the course of the disease, patients eventually become refractory to the various treatments. Therefore, new therapeutic options which utilize new mechanisms of action are essential. Melphalan flufenamide (melflufen) represents such an additional therapeutic approach. Melflufen is a peptide-drug conjugate (PDC) which is highly lipophilic and rapidly incorporated into the tumor cells. Once inside the tumor cell, melflufen is hydrolyzed by peptidases, including aminopeptidases and esterases, to release its alkylator payload. The alkylating agent then induces DNA damage resulting in cell death. Melphalan flufenamid in combination with Dexamethason was approved by the European Medicines Agency (EMA) in August 2022 for the treatment of patients with triple class refractory relapsed/refractory Multiple Myeloma who have received at least 3 prior lines of therapy. For patients with prior autologous stem cell transplantation, the time to progression should be at least 3 years from transplantation. The non-interventional study MARINA aims to address open scientific questions regarding the effectiveness, as well as therapy and safety management of melflufen in a real-world setting. By collecting comprehensive real-world data - including the Disease Control Rate (DCR) as a key endpoint, which is of most value for patients in this late disease stage - MARINA will investigate the therapeutic benefit of melflufen in routine clinical practice.
Interventions
None listed
Sponsors
iOMEDICO AG
Oncopeptides AB
Study design
Observational model
COHORT
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Patients with R/RMM who have previously been treated with at least one proteasome inhibitor, one immunomodulatory agent, and one anti-CD38 monoclonal antibody, and who relapsed on or after the last therapy * Indication and decision for fourth- or later-line treatment with melflufen (Pepaxti®) and dexamethasone, according to current SmPC as assessed by the treating physician * Signed and dated written informed consent\*. * Treatment decision before inclusion into this non-interventional study * Age ≥18 years * Patients are allowed to be enrolled up to 28 days (+ 14 days) after their first dose of melflufen+dexamethasone,, but before any response assessment and second dose of melflufen+dexamethasone. These patients will not participate in the PRO assessments.
Exclusion criteria
* Participation in an interventional clinical trial (except follow-up) * Patient unable to consent * Contraindications according to current SmPC
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Disease control rate (DCR) | max. 38 months (FPI - LPLV) | DCR is defined as the proportion of patients achieving a remission (i.e., sCR, CR, VGPR or PR or MR) or stable disease as best response according to local medical standards during treatment with melflufen. Patients without response measurement are considered non-responders. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Progression-free survival (PFS) | max. 38 months (FPI - LPLV) | PFS is defined as the time from start of melflufen treatment until first progression or death from any cause, whichever comes first. Patients without disease progression or death at the time of analysis will be censored at their date of last contact. PFS will be calculated using the Kaplan-Meier method. |
| Overall survival (OS) | max. 38 months (FPI - LPLV) | OS is defined as the time from start of melflufen treatment until death from any cause. Patients without documented death will be censored with their date of last contact. OS will be calculated using the Kaplan-Meier method. |
| Overall response rate (ORR) | max. 38 months (FPI - LPLV) | ORR is defined as the proportion of patients achieving a remission (sCR, CR, VGPR or PR or MR) as best response according to local medical standards. Patients without response measurement are considered non-responders. |
| Duration of treatment with melflufen | max. 38 months (FPI - LPLV) | Duration of melflufen treatment will be calculated in weeks as the time from first application to the last documented application of melflufen. |
| Clinical benefit rate (CBR) | max. 38 months (FPI - LPLV) | CBR is defined as the proportion of patients achieving a sCR, CR, VGPR, PR or MR as best response according to local medical standards during treatment with melflufen. Patients without response measurement are considered non-responders. |
| Time to next treatment (TTNT) | max. 38 months (FPI - LPLV) | TTNT is defined as the time from start of melflufen treatment until start of the following therapy line or death, whichever comes first. Patients alive and without subsequent treatment at the time of analysis will be censored at their date of last contact. TTNT will be calculated using the Kaplan-Meier method. |
| PFS2 | max. 38 months (FPI - LPLV) | PFS2 is defined as the time from start of melflufen treatment until progression or death during first subsequent treatment line, whichever comes first. If subsequent line is not reached, previous-line death will serve as event. Patients without progression after the start of the subsequent line or death at the time of analysis will be censored at their date of last contact. PFS2 will be calculated using the Kaplan-Meier method. |
| PFS of first subsequent treatment line | max. 38 months (FPI - LPLV) | PFS of first subsequent treatment line is defined as time from start of first subsequent treatment line until first progression thereafter, or death from any cause, whatever comes first. Patients without progression or death at the time of analysis will be censored with their date of last contact. PFS of first subsequent treatment line will be calculated using the Kaplan-Meier method. |
| (Serious) adverse events ((S)AE) | max. 38 months (FPI - LPLV) | The case- and patient-based incidence of (S)AEs will be provided. |
| (Serious) adverse drug reactions ((S)ADR) related to melphalan flufenamid | max. 38 months (FPI - LPLV) | The case- and patient-based incidence of (S)ADRs will be provided. |
| Types of treatments prior to Melflufen | max. 38 months (FPI - LPLV) | To illustrate the prior treatments, the substances administered before Melflufen are listed by treatment line. |
| Melfalan flufenamid starting dose | max. 38 months (FPI - LPLV) | Frequencies of patients with specific melflufen starting dose (i.e., 40mg, 30mg, other) will be provided. |
| Absolute dose intensity of melphalan flufenamid | max. 38 months (FPI - LPLV) | Absolute dose intensity of melphalan flufenamid will be displayed with descriptive statistics. |
| Relative dose intensity of melphalan flufenamid | max. 38 months (FPI - LPLV) | Relative dose intensity of melphalan flufenamid will be displayed with descriptive statistics. |
| Type of dose modifications | max. 38 months (FPI - LPLV) | Type of dose modifications will be displayed with descriptive statistics. |
| Frequency of dose modifications | max. 38 months (FPI - LPLV) | Frequency of dose modifications will be displayed with descriptive statistics. |
| Reasons for dose modifications | max. 38 months (FPI - LPLV) | Reasons for dose modifications will be displayed with descriptive statistics. |
| Substances of subsequent antineoplastic treatment | max. 38 months (FPI - LPLV) | Frequencies of substances used will be displayed in a summary table. |
| Global health-related quality of life during course of treatment | max. 38 months (FPI - LPLV) | The change from baseline (i.e., difference) in the scales of the EORTC QLQ-C30 (European Organisation for Research and Treatment of Cancer quality of life questionnaire C30) will be displayed for each point in time, using boxplots. |
| Multiple myeloma related quality of life during course of treatment | max. 38 months (FPI - LPLV) | The change from baseline (i.e., difference) in the scales of the EORTC QLQ-MY20 (European Organisation for Research and Treatment of Cancer quality of life questionnaire MY20) will be displayed for each point in time, using boxplots. |
| Assessing parameters of physician treatment decision making | max. 38 months (FPI - LPLV) | Results of therapy decision questionnaires will be displayed with frequencies in a summary table. |
Countries
Germany
Contacts
CONTACTSina Grebhardt, PhD
Outcome results
None listed